The Harbor-UCLA Research and Education Institute is highly qualified to be a vigorous and committed site in the COPD Clinical Research Network. The Principal Investigator leads 10 investigators and 3 consultants with broad experience in COPD clinical research. The research facilities are arrayed around a 4000 ft 2 Clinical Trials Center dedicated to COPD research, and include this institution's NIH-supported GCRC. This Center has extensive experience in recruiting COPD patients for both single and multi-center research protocols. Referral resources are solidly in place and have led to success in recruiting a gender-balanced and multi-ethnic population for COPD trials. A total of 20 clinical trials in COPD have been completed in the past two years or are underway. This site is able to perform a wide range of procedures that might be utilized in the network's trials, with special expertise in physiologic testing. We target two especially poor-prognosis COPD groups: chronically hypoxemic patients and patients with weight loss. Both trials focus on determining whether treatments we propose alter survival, though a range of other outcomes will be explored. Protocol 1 is based on the observation that expert opinion holds that lightweight ambulatory oxygen supply is of benefit to hypoxemic COPD patients even though most patients, in practice, are supplied with much heavier E-cylinders. A randomized 18-month trial involving 252 patients will determine whether, compared to patients receiving E-cylinders, patients assigned to lightweight oxygen supply will have increased activities of daily living, use more hours of oxygen per day, have better retention of muscle mass and exercise tolerance, have fewer exacerbations and lower medical resource utilization and, ultimately, have superior survival. Protocol 2 recognizes recent work suggesting that prognosis of underweight COPD patients is improved by weight gain and that muscle dysfunction is a reversible cause of exercise intolerance. We build on our recent demonstrations that testosterone increases muscle mass and strength in COPD men and that megestrol acetate stimulates appetite and increases body weight in COPD. A double-blind, placebo-controlled study involving 225 underweight COPD men is proposed in which 3 groups receive 6 months of 1) placebo, 2) testosterone enanthate 150mg/wk, or 3) testosterone plus megestrol acetate 800mg/day, each for 6 months followed by 12 months of observation. We will determine whether these interventions increase lean and total body mass, decrease systemic inflammation, increase activities of daily living, muscle strength, exercise endurance and quality of life, and thereby improve survival. These studies should have immediate impact on treatment strategies for large poor-prognosis subgroups of COPD patients.